rs751389109

Variant names:

• chr8-55103051-C-G
• rs751389109
• NM_052898.2:c.563C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-55103051-C-G
• chr8-55103051-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052898.2(XKR4):​c.563C>G​(p.Pro188Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P188L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: XKR4 NM_052898.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 0 publications found

Genes affected

XKR4 (HGNC:29394): (XK related 4) Enables phospholipid scramblase activity. Involved in phosphatidylserine exposure on apoptotic cell surface. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22977608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052898.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR4	NM_052898.2	MANE Select	c.563C>G	p.Pro188Arg	missense	Exon 1 of 3	NP_443130.1	Q5GH76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR4	ENST00000327381.7	TSL:1 MANE Select	c.563C>G	p.Pro188Arg	missense	Exon 1 of 3	ENSP00000328326.5	Q5GH76

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000812 AC: 2 AN: 246272 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000906

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460462 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726566

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111726

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000825 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.018
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.97	L
PhyloP100		2.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.67	N
REVEL	Uncertain	0.33
Sift	Benign	0.034	D
Sift4G	Benign	0.60	T
Polyphen		0.41	B
Vest4		0.25
MutPred		0.57		Gain of solvent accessibility (P = 0.0216)
MVP		0.22
MPC		1.7
ClinPred		0.52	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.38
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751389109; hg19: chr8-56015611;